Mechanisms of asthma and allergic inflammation
Downmodulation of CXCL8/IL-8 receptors on neutrophils after recruitment in the airways

https://doi.org/10.1016/j.jaci.2004.08.048Get rights and content

Background

CXCL8/IL-8 is the most significant chemokine for neutrophils, and CXC chemokine receptor (CXCR) 1 and 2 are its 2 receptors, which are downmodulated by CXCL8/IL-8 and endotoxin on activated neutrophils.

Objective

We sought to evaluate the expression of the CXCL8/IL-8 receptors and the activation marker CD11b on neutrophils in peripheral blood and in the site of airway inflammation.

Methods

The flow cytometric expression of CXCR1, CXCR2, and CD11b was evaluated on peripheral blood and induced sputum neutrophils in patients with nonsevere asthma with greater than 60% sputum neutrophils, in patients with chronic obstructive pulmonary disease (COPD), and in healthy control subjects.

Results

Asthmatic patients and patients with COPD had comparable expressions of CXCR1, CXCR2, and CD11b on peripheral blood and sputum neutrophils. Compared with control subjects, the peripheral neutrophil expression of CXCR2 was lower in patients with COPD (P = .03) and that of CD11b was higher in asthmatic patients and patients with COPD (P < .02 and P < .002). The expression of the CXCL8/IL-8 receptors on sputum neutrophils was markedly lower than on peripheral blood neutrophils (P < .0001). The downmodulation of CXCL8/IL-8 receptors was also present in healthy control subjects but less than that seen in asthmatic patients. The difference between peripheral blood and sputum expression of CXCL8/IL-8 receptors correlated with serum CXCL8/IL-8 levels. In asthmatic patients the expression of CXCR1 and CXCR2 on sputum neutrophils negatively correlated with sputum neutrophils.

Conclusion

In neutrophilic asthma the expression of CXCL8/IL-8 receptors on peripheral and sputum neutrophils is similar to COPD and negatively correlated with the inflammatory infiltrate in the airways. The downmodulation of CXCL8/IL-8 receptors detected in the airways should be taken into account for an eventual therapeutic inhibition of these receptors.

Section snippets

Patients

Thirty-four subjects were enrolled in the study: 10 patients with intermittent to moderate-persistent asthma selected to have a percentage of sputum neutrophils greater than 60%, 13 patients with COPD, and 11 healthy control subjects (control group 1). The cutoff point of 60% was chosen because it was greater than the mean ± 2 SD of the normal range we use in our laboratory (27.3% ± 13.0%).12 The characteristics of the subjects enrolled are reported in Table I. COPD and asthma were defined

Soluble mediator levels in asthmatic patients and patients with COPD

To confirm that the asthmatic patients selected had prominent neutrophilic inflammation and eosinophilic inflammation comparable with that of patients with COPD, we evaluated CXCL8/IL-8, MPO, and ECP levels in serum and sputum supernatant. As reported in Table II, serum CXCL8/IL-8 and ECP levels were comparable between the 2 groups of patients, and serum MPO levels were lower in asthmatic patients than in patients with COPD. Compared with healthy control subjects, serum ECP levels were higher

Discussion

In this study we analyzed and compared the in vivo membrane expression of CXCL8/IL-8 receptors and CD11b, a marker of neutrophil activation, on peripheral blood and sputum neutrophils in asthmatic patients with a high amount of neutrophils in the airways and in patients with COPD, for whom there is a great body of evidence in the literature reporting activated airway neutrophils. These data were compared with those obtained in healthy control subjects. To the best of our knowledge, this is the

References (29)

  • A. Jatakanon et al.

    Neutrophilic inflammation in severe persistent asthma

    Am J Respir Crit Care Med

    (1999)
  • S. Sur et al.

    Sudden-onset fatal asthma. A distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa?

    Am Rev Respir Dis

    (1993)
  • J.V. Fahy et al.

    Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation

    J Allergy Clin Immunol

    (1995)
  • S.E. Wenzel et al.

    Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics

    Am J Respir Crit Care Med

    (1999)

    • Cited by (0)

    View full text
    Copyright © 2005 American Academy of Allergy, Asthma and Immunology. Published by Mosby, Inc. All rights reserved.